Evidence map›Paper›PMID 26979312›Full record

Trial reportBreast cancer research : BCR2016

Phase 1b/2a study of trastuzumab emtansine (T-DM1), paclitaxel, and pertuzumab in HER2-positive metastatic breast cancer.

Ian E Krop, Shanu Modi, Patricia M LoRusso, Mark Pegram, Ellie Guardino, Betsy Althaus, Dan Lu, Alexander Strasak, Anthony Elias

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase IClinical Trial, Phase IIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Breast cancer research : BCR, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00951665 (A Phase Ib-IIa, Open-label, Dose-Escalation Study of the Safety, Tolerability and Pharmacokinetics of Trastuzumab Emtansine, Paclitaxel and Pertuzumab Administered Intravenously to Patients With Her2-positive, Locally Advanced or Metastatic Breast Cancer), which is not on this map. Cited by 32 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 3 pooled it
2.8field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00951665 phase1 / phase2completednot on this map

A Phase Ib-IIa, Open-label, Dose-Escalation Study of the Safety, Tolerability and Pharmacokinetics of Trastuzumab Emtansine, Paclitaxel and Pertuzumab Administered Intravenously to Patients With Her2-positive, Locally Advanced or Metastatic Breast Cancer

TypeinterventionalSponsorGenentech, Inc.Ran2009 to 2013Enrolled107ConditionsMetastatic Breast CancerArmspaclitaxel, pertuzumab [Perjeta], trastuzumab emtansine [Kadcyla]
3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 3 syntheses or guidelines pooled it, 48 citations in OpenAlex.

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  14. Antibody-drug conjugates combinations in cancer treatment.Exploration of targeted anti-tumor therapy · 2024
    Review
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  16. Antibody-drug conjugates come of age in oncology.Nature reviews. Drug discovery · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 6 institutions in 2 countries.

Ian E KropBreast Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA, 02215, USA. Ian_Krop@dfci.harvard.edu.
Shanu ModiMemorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
Patricia M LoRussoYale University, 800 Howard Ave, New Haven, CT, 06519, USA.
Mark PegramStanford Cancer Institute, Stanford University School of Medicine, 900 Blake Wilbur, Stanford, CA, 94305, USA.
Ellie GuardinoGenentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.
Betsy AlthausGenentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.
Dan LuGenentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.
Alexander StrasakF. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, Basel, ch-4070, Switzerland.
Anthony EliasUniversity of Colorado Cancer Center, 1665 Aurora Ct, Aurora, CO, 80045, USA.
Dana-Farber Cancer Institute · USMemorial Sloan Kettering Cancer Center · USRoche (Switzerland) · CHStanford University · USUniversity of Colorado Cancer Center · USYale University · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

backgroundIn pre-clinical studies, the anti-tumor activity of T-DM1 was enhanced when combined with taxanes or pertuzumab. This phase 1b/2a study evaluated the safety/tolerability of T-DM1 + paclitaxel ± pertuzumab in HER2-positive advanced breast cancer.

methodsIn phase 1b (n = 60), a 3 + 3 dose-escalation approach was used to determine the maximum tolerated dose (MTD) of T-DM1 + paclitaxel ± pertuzumab. The primary objective of phase 2a was feasibility, with 44 patients randomized to T-DM1 + paclitaxel ± pertuzumab at the MTD identified in phase 1b.

resultsThe MTD was T-DM1 3.6 mg/kg every three weeks (q3w) or 2.4 mg/kg weekly + paclitaxel 80 mg/m(2) weekly ± pertuzumab 840 mg loading dose followed by 420 mg q3w. Phase 2a patients had received a median of 5.0 (range: 0-10) prior therapies for advanced cancer. In phase 2a, 51.2 % received ≥12 paclitaxel doses within 15 weeks, and 14.0 % received 12 paclitaxel doses by week 12. Common all-grade adverse events (AEs) were peripheral neuropathy (90.9 %) and fatigue (79.5 %). A total of 77.3 % experienced grade ≥3 AEs, most commonly neutropenia (25.0 %) and peripheral neuropathy (18.2 %). Among the 42 phase 2a patients with measurable disease, the objective response rate (ORR) was 50.0 % (95 % confidence interval (CI) 34.6-65.4); the clinical benefit rate (CBR) was 56.8 % (95 % CI 41.6-71.0). No pharmacokinetic interactions were observed between T-DM1 and paclitaxel.

conclusionsThis regimen showed clinical activity. Although there is potential for paclitaxel to be added to T-DM1 ± pertuzumab, peripheral neuropathy was common in this heavily pretreated population.

trial registrationClinicalTrials.gov NCT00951665 . Registered August 3, 2009.

Indexed as

Ado-Trastuzumab EmtansineAdultAgedAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsFemaleHumansMaximum Tolerated DoseMaytansineMiddle AgedPaclitaxelTrastuzumabAdo-Trastuzumab EmtansineAntibodies, Monoclonal, HumanizedMaytansinePaclitaxelpertuzumabTrastuzumab

Identifiers

PMID26979312
PMCPMC4791863
OpenAlexW2300014187

What OpenQuestion holds

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LicenceCC BY
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.